Fatigue to fracture medical device testing method and system

ABSTRACT

A method of determining the endurance limit of an implantable medical device is disclosed. The method utilizes a mock vessel that has a compliance that is higher or lower than the normal compliance of a human vessel for which the device is to be used. The device is deployed into the mock vessel and a curable liquid is used to form a layer over the device on the surface of the lumen of the mock vessel. High pressure pulsatile pressurization is applied to the lumen of the mock vessel to cause a failure of the implantable medical device. The amount and cycles of pressure necessary to cause a failure may be used to determine the endurance limit of the implantable medical device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of and claims the benefit of U.S.patent application Ser. No. 15/424,689 filed Feb. 3, 2017, which claimedthe benefit of U.S. Patent Application Ser. No. 62/291,192 filed Feb. 4,2016, the disclosures of which are incorporated herein by reference.

BACKGROUND

The invention generally relates to systems and methods for fatigue orstress testing to fracture one or more implantable medical devices suchas the mesh grid tubes used for implantable medical stents. Morespecifically, the invention relates to systems and methods for stressinga stent or mesh tube to fracture or break which provides valuable datafor estimating the usable life of such devices.

Modern medical procedures routinely include the employment ofimplantable devices into a patient's vascular system to perform varioustherapeutic functions. Prosthetic vascular implants, such asheart-valves, stents, grafts, mesh tubes, and stent-grafts used forhuman implantation are subjected to the continuous fluctuating stress ofblood pressure. As an example, tubular mesh samples or stents are ofteninserted in an artery of a patient to maintain a flow lumen through theartery at a location that had previously been at least partially blockedor occluded. It is therefore necessary to test such implants to provetheir durability over a lifetime of exposure to pulsatile bloodpressure. Ideally such stents, mesh samples, or other vascularprostheses, are able to withstand the physiological dynamics that occurwithin the vessel or organ in which they are emplaced. For instance, inthe abdominal aorta, blood pressure in the average healthy subject is120 mm Hg/80 mm Hg, i.e. the blood pressure varies by 40 mm Hg for everypulse. Compliance of a healthy aorta can be of the order of 20-25% per100 mm Hg so that a change in vasculature diameter of 8 to 10% can beexpected at every heartbeat. In order to simulate such a change indiameter, testers employ a pulse pressure between 80 mm Hg and 100 mmHg. The vessel (artery, vein, etc) in the human body where animplantable medical device is to be implanted is referred to as thetarget human vessel.

One widely used methodology of testing implantable medical devices isreferred to as “testing-to-success”. Typically, in testing-to-success,vascular implants are tested for 400,000,000 cycles which representapproximately 10 years of implantation life at a heart rate of 80 beatsper minute. Testing-to-success is indicative of the durability of thestent under physiological conditions of systolic/diastolic pressuresencountered in accelerated radial pulsatile durability testing. However,testing-to-success does not predict the endurance limit or fatigue lifeof the stent or other implantable device, i.e., there is no way to knowunder what conditions, including conditions that may exceedphysiological parameters, the stent or stent graft would fail. Theendurance limit, also referred to as the fatigue limit, is a well-knownconcept in stress testing and materials science.

To address this weakness in the “testing-to-success” methodology, newregulations (FDA, ASTM, ISO) are being developed that outline testrequirements that are now concerned with predicting fatigue limits ofthe stent or stent graft and require stent manufacturers to test theirproducts under a ‘testing to failure’ or ‘test to fracture’ regime, sothat stents and stent grafts may be tested up to their endurance limit.An alternative method that is being rapidly pursued and evaluated is a“fatigue-to-fracture” approach. This testing methodology involves acombination of finite element analysis modeling and in vitro testing toassess the durability of stents or other implantable through establishedfracture mechanics techniques, such as use of a Wöhler curve, toidentify the endurance/fatigue limit of a device. These testingguidelines and standards are still under development, i.e. ASTMF04.30.06.

Knowing when and where fracture, secondary fracture, or other failure,of the stent, mesh tubes, or other prosthesis, is most likely to occurunder a variety of simulations is ideal to device development.Manufacturers can then use this information to redesign their productwith the knowledge gained by fatigue to fracture analysis. Theoccurrence of the foregoing described fracture or other failure isreferred to herein as a failure event. Providing a stent, or otherprosthesis, of suitable strength and durability for lasting implantationinto a patient, to minimize the likelihood of failure is desirable.Determining the fatigue and endurance limits of the stent, or otherprosthesis, helps accomplish the provision of a suitable stent, or otherprosthesis.

SUMMARY OF THE INVENTION

Other objects and advantages of this invention will become apparent fromthe following description taken in conjunction with the accompanyingdrawings wherein are set forth, by way of illustration and example,certain embodiments of this invention.

In accordance with the present invention, a vascular prosthesis testerfor inducing mechanical stresses upon a vascular prosthesis having atubular channel, or lumen, extending along a longitudinal axis isprovided.

In one embodiment, a method for testing fatigue to fracture by means ofenhanced radial compression of a tubular mesh medical implant comprisesthe steps of: providing a mock vessel that has a lower than normalcompliance; deploying the medical implant within the mock vessel;loading the mock vessel and implant into a testing unit; repeatedlyexpanding the mock vessel and medical implant therewithin using apressurized fluid; providing a high speed camera to monitor thedeflection of the test sample by direct visualization of the medicalimplant to ascertain the time of initial failure or fracture. It isforeseen that the testing unit controls at least one of the followingparameters: temperature, pH, frequency of pulsation of the pressurizedfluid, minimum pressure, and maximum pressure.

The preferred compliance of the mock vessel in this method may bebetween 1% and 2% per 100 mm Hg. It is foreseen that the pressurizedfluid is at least one of air, a saline solution, or distilled water. Thefrequency of expansion of the mock vessel and medical implant may bebetween 1 to 150 Hz but more preferably between 20 and 40 Hz for optimaltesting of a typical implantable vasculature stent.

In one embodiment, the implant is a vascular graft or endovascularprosthesis or common mesh stent with an internal diameter from 2 to 50mm.

In another embodiment of the invention, a method for testing fatigue tofracture by radial expansion of a medical implant comprises the stepsof: providing a mock vessel that has a higher than normal compliance;positioning a tubular medical implant over the mock vessel; loading themock vessel and implant into a testing unit; repeatedly expanding themock vessel and medical implant from within using a pressurized fluid;providing a high speed camera to monitor the deflection of the testsample by directly visualization of the medical implant to ascertain thetime of initial failure or fracture.

In yet another embodiment, the medical implant fatigue is tested using acombination of enhanced radial compression and enhanced radialexpansion. The combination testing comprises the steps of providing amock vessel having lower than normal compliance; positioning a tubularmedical implant within the mock vessel; placing an inner liner tubewithin the mock vessel to substantially capture the tubular medicalimplant between the outer periphery of the inner liner tube and theinner wall of the mock vessel; loading the mock vessel, implant andinner liner tube into a testing unit; repeatedly expanding the mockvessel and medical implant from within the inner liner tube from withinusing a pressurized fluid; providing a high speed camera to monitor thedeflection of the test sample by directly visualization of the medicalimplant to ascertain the time of initial failure or fracture. The firstinner liner tube may have an outer diameter that is from between 85% to95% of an inner diameter of the mock vessel.

In another embodiment, the inner liner tube is made from a liquidplastic, such as silicone, that has been cured within the mock vessel tosubstantially encapsulate the medical implant.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top perspective view illustrating a durability testapparatus for fatigue to fracture according to the present invention;

FIG. 2A is an enlarged side view of FIG. 1 with portions cut awayillustrating a first embodiment of the present invention, wherein a mockartery has lower than normal compliance and a mesh stent loaded withinthe mock artery;

FIG. 2B is an enlarged side view of FIG. 1 with portions cut awayillustrating a second embodiment of the present invention, wherein amock artery has a normal compliance with a mesh stent having first andsecond inner liners deployed within;

FIG. 2C is an enlarged side view of FIG. 1 with portions cut awayillustrating a third embodiment of the present invention, wherein a mockartery has a normal compliance with a mesh stent loaded having an innerliner made from silicone;

FIG. 2D is an enlarged side view of FIG. 1 with portions cut awayillustrating a fourth embodiment of the present invention, wherein amock artery has a lower normal compliance with a mesh stent loadedhaving an inner liner;

FIG. 3 is a cross section view of FIG. 2B taken along the line 3-3;

FIG. 4 is a flow diagram of a method in a first embodiment according tothe present invention;

FIG. 5 is a flow diagram of a method in a first embodiment according tothe present invention;

FIG. 6 is a flow diagram of a method in a first embodiment according tothe present invention.

FIG. 7 is a depiction of a Wöhler curve used in fatigue-to-fracturetesting analysis.

DETAILED DESCRIPTION

As required, detailed embodiments of the present invention are disclosedherein; however, it is to be understood that the disclosed embodimentsare merely exemplary of the invention, which may be embodied in variousforms. Therefore, specific structural and functional details disclosedherein are not to be interpreted as limiting, but merely as a basis forthe claims and as a representative basis for teaching one skilled in theart to variously employ the present invention in virtually anyappropriately detailed structure. It is also noted that any reference tothe words top, bottom, up and down, and the like, in this applicationrefers to the alignment shown in the various drawings, as well as thenormal connotations applied to such devices, and is not intended torestrict positioning of the components of the invention in actual use.

Referring to FIG. 1, the reference numeral 100 generally designates afatigue to fracture test apparatus according to the present invention.The fatigue to fracture test apparatus 100 having one or more in-lineconduits for attachment to mock vessels or vascular grafts 106. The mockvessel or conduit 106 will have a compliance or measure of thedistensibility of a chamber expressed as a change in volume per unitchange in pressure. A normal arterial compliance varies greatly anywherefrom approximately 4-5% per hundred millimeters (mm) of Mercury (Hg) inthe smaller arteries and up to 20-30% per hundred millimeters (mm) ofMercury (Hg) in the ascending aorta. It is foreseen that the mockvessels 106 may be made from silicone, Teflon®, Fluorinated EthlenePropylene, PerfluoroAlkoxy, Tygon®, PharmaPure®, Kynar, or other knownfluid handling tubing. It is foreseen that these mock vessels 106 can bestraight, curved, undulated, or bifurcated, and are made to virtuallyany range of compliance for radial testing of stents.

An implantable medical device 104, such as a stent or mesh tube, isdeployed in the mock vessel 106, which in some cases may be referred toas a mock artery, along a longitudinal axis A. A vascular stent-typeimplantable medical device 104 is a small tubular structure commonlymade of a thin layer of one of a few biocompatible and corrosionresistant metals, such as 316L stainless steel, nitinol, or cobalt-basedalloys usually in a crossed lattice like or mesh 106 pattern. Stentshave unique attributes that influence the assessment of theirdurability. First, the overall size of the stent can be quite small;some coronary stents are less than 2.5 mm in diameter and 10 mm inlength. Typical cross-sectional dimensions of a single strut, thefundamental structural unit that forms the stent, are on the order of0.11 mm2. The stent 104 is deployed by compression, so that they can bedelivered into the artery, for example, down to less than 1 mm indiameter. After being delivered to the location of interest in the mockvessel 106, one of two techniques can be used to expand the stent-typeimplantable medical device 104 to its clinically relevant diameter. Thefirst is to use a self-expanding stent 104 made of Nitinol (NickelTitanium) which will expand to a predefined diameter. The secondtechnique is to use a balloon to expand the stent-type implantablemedical device 104 to the indicated diameter. In either case thestent-type implantable medical devices 104 are designed to expand to110% of the inside diameter of the mock vessel 106 at the point ofhighest blood pressure. This is done to ensure that the stent-typeimplantable medical devices 104 do not migrate during the systolicportion of the heartbeat.

A motor or drive 108 moves fluid, such as saline, from the fluid inlet109 to the pump 110 by the action of metal bellows, rolling rubberbellows, a piston or the like. Motor 108 may include, for example, ahydraulic, electrodynamic, AC or servo drive system. The pump 110 mayaccelerate test conditions where, for example, when testing to success,400 million heartbeats may be replicated at a cycle rate ranging fromabout 50-6000 cycles/minute. It is foreseen that testing fatigue tofracture can be done at physiological speeds between 1-2 Hz or ataccelerated speeds between 40 Hz and 60 Hz, but for faster results asaccording to the present invention, testing can be done at acceleratedspeeds and high pressures such as 50 pounds per square inch (psi) orapproximately 2500 mmHg. The use of higher pressure in the mock vesselthen exist in a physiological context is also referred to ashyper-physiological loading conditions.

From pump 110, fluid moves through manifold 112, where pressures beingdelivered to devices 104 are monitored. To simulate blood flow, thepressurized test fluid is delivered in a pulsatile flow, with pressuresmodulated between specific points to mimic systolic and diastolicpressures. Manifold 112 may contain stopcocks or isolation valves (notshown) that allow mock vessels 106 and devices 104 to be isolated,removed, replaced, and/or inspected without draining the entireapparatus 100. The manifold 112 allows test fluid to be pumped throughall samples in a closed loop, ensuring an even temperature and pressuredistribution within all mock vessels 106 and also ensuring the removalof shed particles.

Stopcocks 114 may be disposed downstream of mock vessels 106 to allowthe user to select which mock vessels 106 are open and which are closed.Check valves 116, also known as bleed valves or one-way valves, allowfluid to flow along the path shown by arrow 118, while inhibiting orpreventing backflow during diastole of pump 110 when a pulsatile flow isused for testing. Check valves 116 also help to control the rate of flowthrough elastomeric tubing 120. A tank (not shown), containingimplantable device 104, mock vessels 106, stopcocks 114, check valves116 and tubing 120, may be filled with a heated liquid (not shown), forexample, to simulate body temperature. It is also foreseen that the testfluid exits elastomeric tubing 120 through manifold 124 and is carriedoutward for further processing by tubing 126.

To evaluate the fatigue to fracture, high speed photographicverification of stent fatigue by means of a camera 118 and optionalexternal light source 130, such as a FastCam PCI 1280, is utilized. Theinside wall 123 of the mock vessel 106 may be marked with predeterminedsets of points (not shown) and the outside surface 125 may be markedwith a second predetermined set of points, to create landmarks on thevessel 106 that can be tracked by the camera 118 during pulsation. Whenused, the high speed camera 118 will track the first and secondpredetermined sets of points or landmarks on the stent-type implantablemedical device 104 and the distance between the marks will change as themock vessel 106 expands and contracts. The high speed camera 118constitutes a method of direct observation and direct measurement of thestent-type implantable medical device. In the alternative, landmarks maybe identified on the stent-type implantable medical device 104 itself.

It is foreseen that laser micrometer (not shown) measurements may alsobe added and appropriate to monitor the operating conditions of thetest.

It will be appreciated that FIG. 1 teaches by way of example and notlimitation. The number of system components may be increased ordecreased with respect to what is shown. In one such example, sensors(not shown) providing optional alarm capabilities for temperature, pH,mean pressure, pulsatile pressure, number of cycles, and speed may beincorporated into apparatus 100.

Enhanced Radial Compression Testing: Referring now to FIG. 2A, a mockvessel 106 a is shown with outer diameter 131 a. The mock vessel 106 ahas a lower than normal compliance, which varies likewise to the purposeof the stent-type implantable medical device 104 a to be tested. Themock vessel may have set points 141 a marked on the outer surface 125 aof the mock vessel, to be used with the camera to provide referencepoints for visualizing fracture of the stent-type implantable medicaldevice 104 a. The points 141 a may be between the end 135 a of thedevice 104 a and the opposing end of the device 104 a. It is desirablethat the inner surface of mock vessel 106 a will have an inner diameter130 a in the range of 5%-35% greater than the outer diameter of thestent-type implantable medical device 104 a and between 1-2% change inradius per 100 mm of mercury (Hg). Because of the very low compliance ofthe mock vessel 106 a, the stent-type implantable medical device 104 awill be restrained by the vessel wall from expanding to the designedamount which puts the stent 104 a under compressive forces faster thanunder normal compliance conditions. Stent-type implantable medicaldevices 104 a are typically designed to expand to 110% of the insidediameter of an artery (not shown) at the point of highest bloodpressure, herein illustrated in test situations with a mock vessel 106a. This is done to ensure that the stents do not migrate during thesystolic portion of the heartbeat. The low compliance mock vessel 106 acreates an overload situation wherein radial compression forces areintroduced when high pressure is used to open up and on recoil deliveranother high pressure load to the stent-type implantable medical device104 a. The repetitive compressive pressure associate with the pulsatileflow through the mock vessel 106 a causes greater than normal stress onthe stent-type implantable medical device 104 a and under controlledconditions the stent-type implantable medical device 104 a can be forcedto fail. Testing has shown that failure may originate at an apex of thestent-type implantable medical device 104 a. Once failure occurs at asingle point of the stent, complete failure may follow quickly, commonlywith the mesh stent “unzipping” along a linear path originating at theoriginal point of failure.

Enhanced Radial Expansion Testing: Referring now to FIG. 2B, a mockvessel 106 b with inner surface 123 b and outer diameter 131 b is shown.The mock vessel 106 b has a higher than normal compliance, (i.e. innerdiameter 130 b of mock vessel 106 b is greater than 130 a under fatigueto fracture testing pressures) which varies likewise to the purpose ofthe stent-type implantable medical device 104 b being tested. The mockvessel may have set points 141 b marked on the outer surface 125 b ofthe mock vessel, to be used with the camera to track fracture of thestent-type implantable medical device 104 b. In some embodiments, thetesting configuration for the stent-type implantable medical device 104b includes an inner liner 132 b. In some embodiments, the inner liner132 b is a thin walled tube inserted through the stent-type implantablemedical device 104 b after the stent 104 b has been expanded. It isforeseen that the stent-type implantable medical device 104 b may beexpanded by either a balloon or is made of a self-expanding materialsuch as Nitinol. It is preferred that the inner liner 132 b may be madeof several additional series of layers, and it is not meant to belimited. In some embodiments, liquid pressurization of the mock vessel106 b creates an inner radial expansive pressure or force that embedsthe stent 104 b into the mock vessel 106 b as seen in FIG. 2B. In someembodiments, the inner liners 132 b may be created by coating the innersurface of the mock vessel 106 and stent-type implantable medical device106 b with liquid silicone to create the inner liner 132 b. Thethickness of the liner 132 b can be controlled by the length and numberof applications of liquid silicone. When dried, the siliconesubstantially encapsulates the test stent 104 b to simulateendothelialzation of the stent-type implantable medical device.

The ends 135 b and 137 b of the inner liner stick out further than alength of the stent-type implantable medical device 104 b. It ispreferred that extra dips of silicone (not shown) may be formed on theends 135 b of the inner liner 132 b. In the alternative, sleeves may beformed from low compliant tubing and placed over the ends 135 b of theinner liner 132 b.

Referring to FIG. 3, a cross-sectional view of mock vessel 106 b isdepicted along the axis 3-3 shown on FIG. 2B. Mock vessel 106 b has anouter diameter 131 b and an inner surface 123 b with inner diameter 130b. The mock vessel 106 b is shown with a stent-type implantable medicaldevice 104 b, an inner liner 132 b, and a second inner liner 134 b. Theinner line 132 b has an inner diameter 140 b and an outer diameter of144 b. The inner liner 134 b has an inner diameter of 145 b and an outerdiameter of 146 b. In some embodiments, the inner liner 132 b will havean inner diameter 140 b in the range of ½ to ⅔ the outer diameter 148 bof the stent-type implantable medical device 104 b or between 1-5%change in radius per 100 mm of mercury (Hg) compliance. The inner liner132 b will have an outer diameter 144 b that is 90% of the working innerdiameter 148 b of the stent-type implantable medical device 104 a. Thestent-type implantable medical device 104 a will be forced to expand tothe inner diameter 130 b of the mock vessel 106 b because of the veryhigh compliance of the inner liners 132 b, 134 b, which places thestent-type implantable medical device 104 b under expansive forcesfaster than under normal compliance conditions. The high complianceinner liner 132 b creates an overload condition, as the expansion testrequires high pressure or high frequency pulsatile flow to open up thestent-type implantable medical device 104 b and on recoil deliver a highload to the stent-type implantable medical device 104 b. The mock vessel106 b may have set points 141 b marked on the outer surface 125 b of themock vessel 106 b, to be used with the camera to track fracture of thestent-type implantable medical device 104 b.

Referring now to FIG. 2C, a mock vessel 106 c is shown with innerdiameter 130 c and outer diameter 131 c. The mock vessel 106 c has ahigher than normal compliance, which varies likewise to the purpose ofthe stent-type implantable medical device 104 c being tested. The mockvessel 106 c may have set points 141 c marked on the outer surface 125 cof the mock vessel, to be used with the camera to track fracture of thestent-type implantable medical device 104 c. The stent-type implantablemedical device 104 c further includes an inner liner 152 made from curedliquid silicone. The inner liner 132 c has ends 135 c and 137 c and anouter diameter 144 c. The mock vessel 106 c containing the expandedstent-type medical device 104 c is removed from the tester 100 andfilled with liquid silicone. The liquid silicone sticks to thestent-type implantable medical device 104 c and inner wall 123 c of themock vessel 106 c and may be allowed to drip out of the mock vessel 106c to leave a thin layer of silicone behind. The area where thestent-type implantable medical device 104 c is deployed is cured toharden the silicone creating the inner liner 132 c. It is foreseen thatthe inner liner 132 c may be made of several additional series of layersof silicone, by repeating this process, and it is not meant to be alimiting example. The inner liner 132 c, like the inner liner 132 bexplained above, creates an inner radial expansive pressure or forcethat embeds the stent-type implantable medical device 104 c into themock vessel 106 c. The inner liner liquid may be a silicone basedmaterial, but may also be selected from other materials such as Teflon®,Fluorinated Ethlene Propylene, PerfluoroAlkoxy, Tygon®, PharmaPure®,Kynar, or other known fluids that are capable of hardening into aflexible liner.

Combination Enhanced Radial Compression and Enhanced Radial ExpansionTesting: Referring now to FIG. 2D, a configuration is depicted forgenerating a combination of compressive and expansive forces to beimparted on the stent-type implantable medical device 104 d. A mockvessel 106 d with inner diameter 123 d and outer diameter 131 d is shownwith a lower than normal compliance, which varies likewise to thepurpose of the stent-type implantable medical device 104 d. The mockvessel 106 d may have set points 141 d marked on the outer surface 125 dof the mock vessel, to be used with the camera to track fracture of thestent-type implantable medical device 104 d. It is preferred that themock vessel 106 d will have an inner diameter 130 d in the range of ½ to⅔ the outer diameter 131 d of the stent-type implantable medical device104 d or between 1-2% change in radius per 100 mm of mercury (Hg), andbecause of the very low compliance of the mock vessel 106 d, thestent-type implantable medical device 104 d will not always expand tothe designed amount which places the stent-type implantable medicaldevice 104 d under compressive forces faster than under normalcompliance conditions. After the stent-type implantable medical device104 d is positioned within the mock vessel 106 d an inner liner 132 d isplaced therewithin to capture the stent 104 d between the outer wall ofthe inner liner 132 d and the inner wall of the test vessel. The innerliner 132 d may be a thin walled tube inserted through the stent-typeimplantable medical device 104 d. In some embodiments, the inner liner132 d will have an inner diameter 140 d in the range of ½ to ⅔ thediameter 148 d of the stent-type implantable medical device 104 d orbetween 1-5% change in radius per 100 mm of mercury (Hg) compliance. Theends 135 d of the inner liner 132 d extend beyond the ends of stent-typeimplantable medical device 104 d. The outer diameter 144 d of the innerliner 132 d may between 85-95% of the working inner diameter 148 d ofthe stent-type implantable medical device 104 d. The stent-typeimplantable medical device 104 d will be forced to expand to the innerdiameter 130 d of the mock vessel 106 d because of the very highcompliance of the inner liner 132 d which places the stent-typeimplantable medical device 104 d under expansive forces upon applicationof the pressurized test liquid. The high compliance inner liner 132 d incombination with the low compliance mock vessel 106 d create an overloadcondition, as the expansion/compression test requires high pressure orhigh frequency pulsatile flow to open up the stent-type implantablemedical device 104 d and on recoil deliver a high compression load tothe stent-type implantable medical device 104 d. Repeated compressionand expansive force imparted on the stent-type implantable medicaldevice 104 a during pulsatile flow may embed the stent-type implantablemedical device 104 d to the mock vessel 106 d, as is seen in FIG. 2D.

FIG. 4 is a flow diagram illustrating a method 200 of fatigue tofracture testing using radial compression. At step 210, the inside wallof the mock vessel is marked with predetermined sets of points and theoutside wall is marked with a predetermined set of points, to createlandmarks on the vessel that can be tracked by the camera duringtesting.

At step 212, a mesh tube, stent, or implantable sample is deployed in amock vessel. The stent may be balloon expanded or made from Nitinol andis expanded as it is deployed. The mock vessel has a lower than normalcompliance, i.e. 1% to 2% per 100 mm Hg. At step 214, the mesh tube andmock vessel as a unit are loaded onto a tester unit.

At step 216, the tester is set to deliver pulsatile flow including apredetermined: temperature, pH, pulsation frequency, and maximum andminimum pressure for each cycle.

At step 218, a high speed or still camera is set to monitor thedeflection of the test sample. The high speed camera will track pairs oflandmarks on the stent and the distance between the marks will change asthe mock vessel expands and contracts. It is foreseen that a multitudeof cameras may be necessary to give a full 360 degree view of the meshtube.

At step 220, the tester is set to run at the predetermined parameters.

At step 222, when a break occurs, then at step 224, the number of cyclesto break is determined, and the tester continues to run. When apredetermined number of breaks have been met, then process is ended atstep 226. The whole method is repeated with adjusted parameters togenerate the data necessary to determine fatigue properties of thetested stent.

FIG. 5 is a flow diagram illustrating a method 300 of fatigue tofracture testing using radial expansion.

At step 312, a mesh tube, stent, or implantable sample is deployed ontoa mock vessel. The stent may be balloon expanded or made from Nitinoland is expanded as it is deployed. The mock vessel has a higher thannormal compliance for the test stent deployed.

At step 314, the test vessel has a radial compliance of 5% per 100 mm Hgand that has an outer diameter from between 85% to 95% a working innerdiameter of the stent. The ends of the inner tube extending beyond thepositioned stent may be strengthened by placing low compliance tubingover the ends or by applying a liquid silicone material to the ends ofthe test vessel, and then curing the silicone to harden.

At step 316, the mesh tube and mock vessel as a unit are loaded onto atester unit.

At step 318, the tester is set to deliver pulsatile flow including apredetermined: temperature, pH, pulsation frequency, and maximum andminimum pressure for each cycle.

At step 320, a high speed or still camera is set to monitor thedeflection of the test sample. The stent may have set points 141 markedon the outer surface or specific landmarks may be identified to be usedwith the camera to track fracture of the stent 104 b. The high speedcamera will track landmarks 141 on the stent and the distance betweenthe marks 141 will change as the mock vessel expands, contracts, andfractures. A plurality of cameras may be necessary to give a full 360degree view of the mesh tube.

At step 322, the tester is set to run at the predetermined parameters.

At step 324, when a break occurs then at step 326, the number of cyclesto break is determined, and the tester continues to run. When apredetermined number of breaks have been met, then process is ended atstep 328. The whole method is repeated with adjusted parameters togenerate the data necessary to determine fatigue properties of thetested stent.

FIG. 6 is a flow diagram illustrating a method 400 of fatigue tofracture utilizing a combination of radial expansion and compression. Atstep 410, the inside wall of the mock vessel is marked withpredetermined sets of points and the outside wall is marked with apredetermined of points, to create landmarks on the vessel that can betracked by the camera during testing.

At step 412, a mesh tube, stent, or implantable sample is deployedwithin a mock vessel. The stent may be balloon expanded or made fromNitinol and is expanded as it is deployed. The mock vessel has a lowerthan normal compliance for the test stent deployed, i.e. 1% to 2% per100 mm Hg.

At step 414, insert a higher than normal compliance inner tube that hasa radial compliance of 5% per 100 mm Hg and that has an outer diameterbetween 85-95% of the working inner diameter of the stent deployed. Theinner tube may be formed by applying a liquid silicone material to theinner wall of the test vessel, and then curing the silicone to hardeninto an inner layer. The stent becomes encapsulated within thesilicone-formed wall of the vessel.

At step 416, the mesh tube, inner liner, and mock vessel as a unit areloaded onto a tester unit.

At step 418, the tester is set to deliver pulsatile flow including apredetermined: temperature, pH, pulsation frequency, and maximum andminimum pressure for each cycle. Also, a predetermined number of breaksin the stent are set.

At step 420, a high speed or still camera is set to monitor thedeflection of the test sample. The high speed camera will tracklandmarks on the stent and the distance between the marks will change asthe mock vessel expands and contracts. A plurality of cameras may benecessary to give a full 360 degree view of the mesh tube.

At step 422, the tester is set to run at the predetermined parameters.

At step 424, when a break occurs then at step 426, the number of cyclesto break is determined, and the tester continues to run. When apredetermined number of breaks have been met, then process is ended atstep 428. The whole method is repeated with adjusted parameters togenerate the data necessary to determine fatigue properties of thetested stent.

As described above, the fatigue-to-fracture testing methodology applieshyper-physiological loading conditions to the implantable medical deviceto cause a failure event to occur within a relatively short time frame.The loading conditions are then altered and the test is repeated onadditional test articles of an implantable medical device. Somepreferred embodiments of the foregoing method are described in detailbelow.

In some preferred embodiments, test articles of the implantable medicaldevice is deployed into a set of mock vessels having a compliance of 2%per 100 mmHg when tested at typical physiological conditions. The mockvessels are then filled with liquid silicone, and the liquid siliconewas allowed to drain from a first end of the lumens of each mock vesselto create the inner layer. The mock vessels are then filled with liquidsilicone and allowed to drain from the second end of the lumens tocreate an additional inner layer. One or more of the mock vessels withtest articles are then placed into a testing system such as describedabove, and the lumens are filled with a pressurized fluid with apulsatile pressure at hyper-physiological conditions to induce failureof the test articles of the implantable medical device.

In some preferred embodiments of the method, the pulsatile pressure willbe applied for a predetermined set of cycles and then the pressures areincreased in a staircase method to cause failure. In a preferredembodiment of the method, the test articles are subjected to 10⁶ cyclesat either 30 Hz or 60 Hz before the pressure is increased to the nextlevel. In a preferred embodiment, the hyper-physiological pressurelevels utilized are 500±40 mmHg, 500±100 mmHg, 500±200 mmHg, 500±300mmHg, 500±400 mmHg, and 750±500 mmHg. In another preferred embodiment,the hyper-physiological pressure levels utilized are 500±150 mmHg,500±200 mmHg, 500±250 mmHg, 500±300 mmHg, 500±400 mmHg, 500±400 mmHg,and 750±500 mmHg. The ± values indicate the range of the pulsatilepressure change during testing. During testing each test article iscontinuously or periodically checked for failure, and the cycles tofailure are determined at varying levels of precision. When a testarticle fails it may be removed from the testing system or disconnectedfrom the pulsatile pressure. In a preferred embodiment, the testarticles are checked for failure at each change in the pressuresettings. The pressures used in the iterations of the testing areselected to characterize the endurance limit of the implantable medicaldevice using fatigue-to-fracture techniques. The increasing staircasemethod described in this paragraph may be used to determine the relevantpressure range for the fatigue-to-fracture testing for a specificimplantable medical device.

In other preferred embodiments of the method, the pulsatile pressurewill be applied for a predetermined set of cycles and the pressures arethen decreased. In preferred embodiments, the hyper-physiologicalpressure levels utilized in the test are 750±500 mmHg, 500±450 mmHg,500±425 mmHg, 500±400 mmHg, 500±300 mmHg, 500±200 mmHg, and 500±150mmHg. In this method the test articles are subjected to each pressurelevel for 10⁷ cycles or until failure is detected. Each test article isintermittently checked for failure during testing cycle. In a preferredembodiment of this method, each test article is checked for failureafter 100,000, 180,000, 320,000, 560,000, 10⁶, 1.8×10⁶, 3.2×10⁶,5.6×10⁶, and 10⁷ cycles. In other embodiments, the test articles may bechecked for failure at higher or lower frequencies. The cycles andpressures at which failures occurred are recorded, and test articlesthat survived all testing pressures are considered “runout”. The datacollected by these methods may be used to characterize the endurancelimit of the implantable medical device using known methods of analysissuch as the Wöhler curve method described below.

In additional preferred embodiments, one or more additional mock vesselswith test articles are placed into a testing system, and the lumens arefilled with a pressurized fluid with a pulsatile pressure at one or moreselected hyper-physiological conditions to induce failure of the testarticles of the implantable medical device at a variety ofhyper-physiological conditions. The pressures and frequencies used inthe iterations of the testing may be selected to further characterizethe endurance limit of the implantable medical device based oninformation collected in prior testing cycles. For example, pressureamplitudes between previously tested amplitudes may be tested to addfurther definition to a Wöhler curve.

In a preferred embodiment of the inventive method described above, knowntechniques for analyzing data collected during fatigue-to-fracture testsare utilized to characterize the endurance limit of an implantablemedical device. One well known method of characterizing the endurance orstress limit of a device is a Wöhler curve such as that shown on FIG. 7.The depicted graph of the results of an exemplary fatigue-to-fracturetest are depicted. The graph depicts the horizontal axis (abscissa) ofcycles to failure versus the vertical axis (ordinate) of test pressure.This type of stress versus cycles graph may be used to produce a Wöhlercurve to characterize the materials performance of a test article, inthis case an implantable medical device.

In the depicted graph 700, the average cycles-to-failure 702, 704, 706,and 708 at each pressure are plotted. Runout values 710 and 712 may alsobe plotted to show that no failures occurred at certain pressures. Agraph of the trend of the data points from the testing may be used tofit a curve 714 to the data, thus estimating the endurance limit 716 ofthe implantable medical device.

In the graph depicted in FIG. 7, the solid data points depict testiterations where the test articles failed. In the depicted graph, datapoint 702 depicts the average cycles to failure for the test articles ata mean test pressure of 500 mmHg. Similarly, data points 704, 706, and708, represent the average cycles to failure for test articles at 450mmHg, 400 mmHg, and 350 mmHg, respectively. Circle data points 710 and712 depict test iterations in which the maximum number of cycles for thetest was reached before the occurrence of any test article failures,which may also be referred to as a runout event.

The data points 702, 704, 706, and 708 may be used to construct alogarithmic curve 714 to fit the data. This logarithmic curve, or Wöhlercurve, 714 helps characterize the horizontal asymptotic value 716 forstress (or in this case baseline pressure) below which a properlyfunction article of the device will never fail. This asymptotic value716 is sometimes referred to as the fatigue limit, the endurance limit,or the fatigue strength of a material. If the endurance limit value 716is greater than the normal physiological loading conditions to which theimplantable medical device will be subjected, then a properlymanufactured article of the device should never fail during use.

In some embodiments of the fatigue-to-fracture methods described herein,average pressures of up to 2,500 mmHg may be utilized, with cyclicpressure differentials of ±500 mmHg or more at rates such as 30 Hz or 60Hz.

Changes may be made in the above methods, devices and structures withoutdeparting from the scope hereof. Many different arrangements of thevarious components depicted, as well as components not shown, arepossible without departing from the spirit and scope of the presentinvention. Embodiments of the present invention have been described withthe intent to be illustrative and exemplary of the invention, ratherthan restrictive or limiting of the scope thereof. Alternativeembodiments will become apparent to those skilled in the art that do notdepart from its scope. Specific structural and functional detailsdisclosed herein are not to be interpreted as limiting, but merely as arepresentative basis for teaching one of skill in the art to employ thepresent invention in any appropriately detailed structure. A skilledartisan may develop alternative means of implementing the aforementionedimprovements without departing from the scope of the present invention.

It will be understood that certain features and subcombinations are ofutility and may be employed without reference to other features andsubcombinations and are contemplated within the scope of the claims. Notall steps listed in the various figures need be carried out in thespecific order described.

The invention claimed is:
 1. A method for determining the endurancelimit of an implantable medical device designed for implantation into atarget human vessel, the method comprising the steps of: providing atleast one mock vessel having a compliance that is lower than the normalcompliance of the target human vessel; deploying one of at least onetest article of the implantable medical device in a lumen of the atleast one mock vessel; applying a curable liquid to the lumen of the atleast one mock vessel to form a liner layer over the at least one testarticle of the implantable medical device; and applying a high pressurepulsatile pressurization to the lumen of the at least one mock vessel atleast until the occurrence of at least one failure event.
 2. The methodof claim 1, wherein the step of applying a curable liquid to the lumenof the at least one mock vessel comprises the steps of: injecting thecurable liquid into the lumen of each of the at least one mock vessel ina quantity sufficient to encapsulate the test article of the implantablemedical device in a layer; and curing the curable liquid to form a solidliner layer.
 3. The method of claim 2, further comprising the step ofrepeating the step of applying a curable liquid to the lumen of the mockvessel to form a second inner layer.
 4. The method of claim 1 furthercomprising the steps of: recording a data set including a pressure valueand a number of cycles associated with each of the at least one failureevent; and determining the endurance limit of the implantable medicaldevice based on the data set.
 5. The method of claim 1 wherein theimplantable medical device is selected from the group consisting of astent, a graft, and a stent-graft.
 6. The method of claim 1, wherein thestep of applying a high pressure pulsatile pressurization to the lumenof the at least one mock vessel at least until the occurrence of atleast one failure event further comprises the steps of: applying a highpressure pulsatile pressurization to the lumen of the at least one mockvessel for a first number of pressurization cycles; inspecting each ofthe at least one test article for a failure; repeating the steps ofapplying and of inspecting until a failure event is identified in atleast one of the test articles or until a maximum number ofpressurization cycles has been applied to the at least one mock vessel.7. The method of claim 1 wherein the liner layer has a compliance thatis higher than the normal compliance of the target human vessel.
 8. Amethod for determining the endurance limit of an implantable medicaldevice designed for implantation into a target human vessel, the methodcomprising the steps of: providing at least one mock vessel having acompliance that is higher than the normal compliance of the target humanvessel; deploying at least one test article of the implantable medicaldevice in a lumen of the at least one mock vessel; applying a curableliquid to the lumen of the at least one mock vessel to form a linerlayer over the at least one test article of the implantable medicaldevice; and applying a high pressure pulsatile pressurization to thelumen of the at least one mock vessel at least until the occurrence ofat least one failure event; recording a data set including a pressurevalue and a number of cycles associated with each of the at least onefailure event; and determining the endurance limit of the implantablemedical device based on the data set.
 9. The method of claim 8, whereinthe step of applying a curable liquid to the lumen of the at least onemock vessel comprises the steps of: injecting the curable liquid intothe lumen of each of the at least one mock vessel in a quantitysufficient to encapsulate the test article of the implantable medicaldevice in a layer; and curing the curable liquid to form a solid linerlayer.
 10. The method of claim 9, further comprising the step ofrepeating the step of applying a curable liquid to the lumen of the mockvessel to form a second inner layer.
 11. The method of claim 8 whereinthe implantable medical device is selected from the group consisting ofa stent, a graft, and a stent-graft.
 12. The method of claim 8, whereinthe step of applying a high pressure pulsatile pressurization to thelumen of the at least one mock vessel at least until the occurrence ofat least one failure event further comprises the steps of: applying ahigh pressure pulsatile pressurization to the lumen of the at least onemock vessel for a first number of pressurization cycles; inspecting eachof the at least one test article for a failure; repeating the steps ofapplying and of inspecting until a failure event is identified in atleast one of the test articles or until a maximum number ofpressurization cycles has been applied to the at least one mock vessel.13. The method of claim 8 wherein the liner layer has a compliance thatis higher than the normal compliance of the target human vessel.
 14. Amethod for determining the endurance limit of an implantable medicaldevice designed for implantation into a target human vessel, the methodcomprising the steps of providing a mock vessel having a compliance thatis higher or lower than the normal compliance of the target humanvessel; deploying a test article of the implantable medical device intoa lumen of the mock vessel; filling the lumen of the mock vessel with acurable liquid; allowing the excess of the curable liquid to drain fromthe lumen to form a cured inner layer; applying a pulsatilepressurization to the lumen of the mock vessel using a fluid until theoccurrence of a failure event.
 15. The method of claim 14 furthercomprising the step of reducing the pressure of the pulsatilepressurization after a fixed number of cycles if a failure event has notoccurred.
 16. The method of claim 15 further comprising the step ofrecording a data set comprising the pulsatile pressurization and thenumber of cycles upon occurrence of a failure event.
 17. The method ofclaim 16 further comprising the step of repeating the steps of claim 16for a plurality of test articles of the implantable medical device in aplurality of mock vessels.
 18. The method of claim 17 wherein theplurality of mock vessels have a compliance that is lower than thenormal compliance of the target human vessel.
 19. The method of claim 18wherein the liner layer in the plurality of mock vessels has acompliance that is higher than the normal compliance of the target humanvessel.
 20. The method of claim 17 wherein the plurality of mock vesselshave a compliance that is higher than the normal compliance of thetarget human vessel.